In the past, “advanced” lipoprotein test panels have typically included a lipoprotein measurement of average low-density lipoprotein (LDL) particle size as well as LDL particle number, the latter representing the concentration or quantity (in concentration units such as nmol/L) and the former representing the average size of the LDL particles (in nm units) making up the LDL in the sample. For example, in the NMR LipoProfile® lipoprotein panel report available from LipoScience, Inc., located in Raleigh, N.C., the average LDL particle size corresponds to the average size of a sample's total LDL particles, i.e., the average size of the combined small, intermediate and large LDL particles. Any one person can have LDL particles present in a continuum of different particle sizes. See www.liposcience.com and U.S. Pat. No. 6,576,471 for exemplary reports of particular lipoprotein subclass parameters, the contents of the patent are hereby incorporated by reference as if recited in full herein.
Generally stated, U.S. Pat. No. 4,933,844, entitled Measurement of Blood Lipoprotein Constituents by Analysis of Data Acquired from an NMR Spectrometer to Otvos and U.S. Pat. No. 5,343,389, entitled Method and Apparatus for Measuring Classes and Subclasses of Lipoproteins, also to Otvos, describe NMR evaluation techniques that concurrently obtain and measure a plurality of different lipoprotein constituents in an in vitro blood plasma or serum sample. See also, U.S. Pat. No. 6,617,167, entitled Method Of Determining Presence And Concentration Of Lipoprotein X In Blood Plasma And Serum. The contents of all the above patents are hereby incorporated by reference as if recited in full herein. To evaluate the lipoproteins in a blood plasma and/or serum sample, the amplitudes of a plurality of NMR spectroscopy derived signals within a chemical shift region of the NMR spectrum are derived by deconvolution of the composite signal or spectrum and are compared to predetermined test criteria to evaluate a patient's risk of having or developing coronary artery or heart disease.
Conventionally, a patient's overall risk of coronary heart disease (CHD) and/or coronary artery disease (CAD), has been assessed based on measurements of cholesterol content of a patient's LDL and HDL particles (LDL-C, HDL-C) rather than the numbers of these particles. These two risk factors are used to assess a patient's risk, and treatment decisions may be made to reduce the “bad” cholesterol (LDL-C) or increase the “good” cholesterol (HDL-C). A convenient combined risk factor is the ratio of LDL-C/HDL-C (or more commonly used is the ratio of Total Cholesterol/HDL-C, which is almost the same thing)—to give an overall assessment of risk based on the relative amounts of LDL and HDL. Many physicians like the simplicity offered by the ratio and it is often used to gauge the success of LDL and/or HDL treatment interventions. If only the ratio is reported, however, the doctor won't know whether to direct therapy to reduce the numerator (LDL) or increase the denominator (HDL). So LDL-C and HDL-C plus the ratio are generally reported. Unfortunately, HDL-C does not adequately reflect the numbers of HDL subclass particles and may not be representative of a person's true HDL-related risk of having or developing CHD. In view of the foregoing, there remains a need to provide improved predictive models for assessing a person's risk of developing or having CHD.